Ascites

Ascites is the abnormal accumulation of fluid within the peritoneal cavity and is a common complication of portal hypertension (e.g., due to liver cirrhosis, acute liver failure) and/or hypoalbuminemia (e.g., due to nephrotic syndrome). Other conditions resulting in ascites include chronic heart failure, inflammation of abdominal viscera (e.g., pancreatitis), and malignancies. Clinical features include progressive abdominal distention, shifting dullness, and a positive fluid wave test. Abdominal pain may be present in ascites due to acute inflammation. Diagnostics are aimed at identifying the underlying etiology and determining whether the ascitic fluid is infected. They include imaging (e.g., with abdominal ultrasound or CT abdomen and pelvis), which is used to identify free intraperitoneal fluid and possibly the underlying cause, and diagnostic paracentesis with ascitic fluid analysis. The serum-ascites albumin gradient (SAAG), or the difference between albumin levels in serum and ascitic fluid, is essential to determine the underlying cause. A high SAAG indicates that the ascites is secondary to portal hypertension. An ascitic fluid neutrophil count ≥ 250 cells/mm³ indicates spontaneous bacterial peritonitis (SBP), which should be urgently managed with empiric antibiotic therapy. Management of ascites involves identifying and managing the underlying cause as well as dietary sodium restriction and diuretic therapy. Additionally, tense ascites and refractory ascites require therapeutic paracentesis. Liver transplant is a treatment option for patients with cirrhosis who develop ascites. Transjugular intrahepatic portosystemic shunts (TIPS) and peritoneovenous shunts are advanced treatment options for refractory ascites, which carries a high risk of mortality.

• Portal hypertension
  • Cirrhosis (most common cause of ascites; approx. 85%)
  • Liver metastases
  • Budd-Chiari syndrome
  • Right heart failure
  • Portal vein thrombosis
• Hypoalbuminemia
  • Nephrotic syndrome
  • Severe malnutrition
  • Protein-losing enteropathy
  • Acute or chronic hepatic failure
• Malignancy
  • Peritoneal carcinomatosis, especially from ovarian, breast, bronchial, gastric, pancreatic, and colorectal carcinoma
  • Lymphomas with peritoneal involvement
  • Liver metastases
• Infection: (e.g., tuberculosis, serositis)
• Pancreatitis

References:^[1][2][3]

The primary mechanism that leads to ascites in cirrhosis is portal hypertension. Hypoalbuminemia can contribute to the formation of, and exacerbate, ascites in cirrhosis.

• Progressive abdominal distention ; symptoms associated with increased abdominal distention include:
  • Early satiety
  • Weight gain
  • Dyspnea
  • Diarrhea, which, if chronic, may manifest with features of malnutrition
  • Abdominal pain may be present
• Flank dullness: typically elicited only if > 1.5 L of ascitic fluid is present ^[6]
• Shifting dullness: change of resonance from dull to tympanic resonance when a patient changes from supine to lateral decubitus position.
• Fluid wave test
  • Wave produced by tapping one side of the abdomen in a patient in supine position
  • This wave will be transmitted to the other side via ascitic fluid.
• Signs of underlying disease
  • Enlarged liver, jaundice, spider angioma, palmar erythema: signs of chronic liver disease
  • Elevated jugular venous pressure, orthopnea, and peripheral edema: heart failure
  • Virchow node and weight loss: abdominal or pelvic malignancy

References:^[2]

Chylous ascites

• Definition: a collection of lymph in the abdominal cavity, which is characteristically triglyceride-rich and has a milky appearance
• Etiology: malignancy (e.g., lymphoma), hepatic cirrhosis, or other lymph disorders (e.g., lymphatic hyperplasia) which result in increased lymph production

Hemorrhagic ascites

• Definition: ascitic fluid in the peritoneal cavity with a RBC count > 50,000 mm^{3 [7]}
• Etiology: : may be spontaneous (e.g., due to peritoneal carcinomatosis or a malignant mass eroding into vessels) or iatrogenic (e.g., following paracentesis or biopsy in patients with cirrhosis)

Pancreatic ascites

• Definition: an accumulation of pancreatic fluid (high amylase levels > 1,000 IU/L) in the peritoneal cavity
• Etiology: pancreatic duct disruption (e.g., an acute attack of pancreatitis, pancreatic surgery and/or trauma), pseudocyst leak/rupture

Diagnostics are used to confirm the presence of ascites, assess the severity, determine the underlying etiology, and evaluate for complications. ^[8]

Imaging ^[9][10]

Abdominal ultrasound with Doppler (initial study of choice)

• Indications
  • Clinical suspicion of new-onset ascites
  • Evaluation for an underlying condition (e.g., cirrhosis, intraabdominal malignancy) ^[11]
  • Ultrasound-guided paracentesis
• Supportive findings
  • Free intraperitoneal fluid
    • Uncomplicated nonhemorrhagic ascites typically appears hypoechoic/anechoic
    • Internal echoes, debris, and septations are suggestive of exudates. ^[10]
  • Features of underlying etiology (e.g., liver cirrhosis, hepatocellular carcinoma, Budd-Chiari syndrome, portal vein thrombosis, ovarian tumors; see respective articles for details)

CT abdomen and pelvis ^[8]

• Indications: to work up for the underlying cause as needed; examples include ^[8][11]
  • GI perforation in patients with postoperative or traumatic ascites
  • Secondary peritonitis
  • Malignancy
• Findings
  • Free intraperitoneal fluid
  • Fluid density depends on the type of ascites

Laboratory studies ^[9]

The choice of laboratory studies should be guided by the pretest probability of the suspected underlying etiology.

• CBC: abnormalities related to an underlying condition
• Coagulation panel: Thrombocytopenia and coagulopathy are signs of advanced liver disease.
• Liver chemistries
  • Elevated transaminases suggest liver disease.
  • Serum albumin (for SAAG calculation)
• BMP
  • Elevated creatinine and BUN: Acute kidney injury is common in patients with decompensated cirrhosis. ^[12]
  • Serum electrolytes: hypervolemic hypotonic hyponatremia (as a complication of cirrhosis) ^[13]
• Additional evaluation for the underlying condition: E.g., see “Diagnostics for cirrhosis.”

Ascitic fluid analysis ^[5][8][9]

Sampling technique

• Obtained via diagnostic paracentesis
• See “Paracentesis” for further details on indications, contraindications, steps, troubleshooting, and complications of this procedure.

Indications

• All patients with new-onset ascites to identify the underlying cause ^[5][6][8]
• Patients at risk of spontaneous bacterial peritonitis (SBP): See “Indications for diagnostic paracentesis in SBP” for details.

Routine peritoneal fluid analysis

• Gross appearance of ascitic fluid: can help determine the underlying cause or complications
  • Transparent to yellow: uncomplicated ascites
  • Cloudy: infection or malignancy
  • Bloody: trauma or malignancy
  • Milky: chylous ascites
  • Dark brown: suggests a biliary leak (e.g., gallbladder perforation)
• Cell count and differential: A neutrophil count ≥ 250 cells/mm³ indicates spontaneous bacterial peritonitis.
• Serum-ascites albumin gradient (SAAG) can be used to differentiate between ascites due to portal hypertension and non-portal hypertensive ascites.
  • SAAG = (albumin levels in serum) - (albumin levels in ascitic fluid)
  • High SAAG ascites: ≥ 1.1 g/dL, indicates portal hypertension with ∼ 97% accuracy. ^[9]
  • Low SAAG ascites: < 1.1 g/dL, indicates non-portal hypertensive ascites.
• Ascitic fluid albumin: for SAAG calculation (obtain same-day serum and ascitic fluid samples)
• Ascitic fluid total protein
  • To differentiate hepatic from cardiac causes in high SAAG ascites
  • To differentiate SBP (typically ≤ 1 g/dL) from secondary peritonitis (typically > 1 g/dL) ^[9][14]

Additional studies

• Suspected infection
  • Microbiology: Gram stain and ascitic fluid culture in blood culture bottles (aerobic and anaerobic) ^[11]
  • Studies to differentiate SBP from secondary spontaneous peritonitis: LDH, glucose, CEA, alkaline phosphatase (see “Spontaneous bacterial peritonitis” for details)
  • Acid-fast bacilli smear and mycobacterial cultures (low sensitivity): only if there is clinical suspicion or a high risk of tuberculous peritonitis
• Suspected malignancy (e.g., peritoneal carcinomatosis)
  • Ascitic fluid cytology
  • Ascitic fluid tumor markers: not routinely recommended for the assessment of malignancy-related ascites
    • Cancer antigen 125 (CA-125): elevated in most patients with ascites regardless of cause
    • Carcinoembryonic antigen (CEA): may be elevated in patients with gastric and intestinal adenocarcinoma ^[11]
• Suspected chylous ascites (milky ascitic fluid): ascitic fluid triglyceride levels > 200 mg/dL indicate chylous ascites ^[15]
• Suspected pancreatic ascites or bowel perforation: elevated ascitic fluid amylase levels suggest pancreatitis or bowel perforation ^[16]

Occult SBP is common in patients with ascites and cirrhosis, and delays in diagnosis increase the risk of death. ^[17]

The International Ascites Club classifies the severity classification of ascites as follows: ^[2]

• Mild ascites (grade 1): ascites only detectable by ultrasound
• Moderate ascites (grade 2): moderate abdominal distention
• Large ascites (grade 3): marked abdominal distention

Approach ^[5][8][9]

• All patients
  • Identify and treat the underlying condition.
  • Therapeutic paracentesis for tense or large ascites
• Patients with cirrhotic ascites
  • Treatment of cirrhosis, including avoidance of certain medications such as NSAIDs and ACE inhibitors
  • Sodium restriction and diuretics are the mainstays of medical and supportive therapy. ^[11]
  • Consider advanced therapies for refractory ascites, e.g., liver transplant.
• Patients with noncirrhotic ascites: treatment of the underlying cause, e.g.
  • Surgery or radiochemotherapy for malignancy
  • Treatment of heart failure
  • Antituberculosis therapy

Obtain hepatology consult for patients with new-onset ascites and known or suspected liver disease.

Medical and supportive therapy ^[5][9][18]

This section details the management of ascites due to cirrhosis. Medical and/or supportive management of other causes of ascites (e.g., heart failure, nephrotic syndrome, peritoneal carcinomatosis, tuberculosis) are outlined in the respective articles for these conditions.

Salt and fluid restriction

• Dietary sodium restriction: 2 g/day or 88 mEq/d (2 g of sodium = 5 g of salt)
  • Recommended for all patients
  • Advise patients to restrict the amount of salt in home-cooked meals and to avoid precooked and prepackaged food.
  • Consider referral to a nutritionist for counseling.
• Fluid restriction: 1 L/day (only if serum Na⁺ < 125 mEq/L)

Diuretics

• Monotherapy with spironolactone may be preferable for new-onset ascites, mild ascites, moderate ascites, and outpatients.
• Combination therapy with spironolactone PLUS furosemide in a 10:4 ratio may be preferable for recurrent gross ascites or when faster resolution of ascites is required (e.g., in hospitalized patients).
• Once ascites is under control, taper to the minimum effective dose to reduce side effects.

Combination diuretic therapy is associated with more rapid ascites reduction and a lower risk of potassium imbalance than monotherapy. ^[11][18]

Diuretics should be used with caution in patients with severe hyponatremia, hepatic encephalopathy, and/or renal function deterioration.

Empiric antibiotic therapy ^[5][9]

Antibiotic therapy for patients with cirrhosis and ascites is recommended in the following situations:

• Patients with GI bleed due to cirrhosis: ceftriaxone until bleeding resolves and vasopressors are discontinued, for a maximum of 7 days
• SBP: See “Empiric antibiotic therapy for SBP” and “SBP prophylaxis.”

Monitoring ^[9][18]

• Monitor weight, blood pressure, nutritional status, serum electrolytes, and renal function.
• Goals of diuretic therapy
  • Patients without peripheral edema: weight loss of up to 0.5 kg/day
  • Patients with significant peripheral edema
    • Maximum recommended weight reduction: 1 kg/day
    • Once edema has resolved, daily weight loss should not exceed 0.5 kg/day
• Discontinue or adjust the dosage of diuretics if adverse effects develop (e.g., hyponatremia, hyperkalemia, renal dysfunction).

Therapeutic paracentesis ^[9][18][19]

See “Paracentesis” for further details on indications, contraindications, steps, troubleshooting, and complications of therapeutic paracentesis.

• Indications
  • Tense or large ascites (first-line)
  • Refractory ascites (can be repeated every ∼ 2 weeks)
  • Malignancy-related ascites
  • Contraindications for diuretic therapy
• Important considerations
  • Perform under ultrasound guidance to minimize complications. ^[20]
  • Replace albumin during or immediately after the procedure to prevent complications, e.g, postparacentesis circulatory dysfunction (PPCD) in: ^[9][21]
    • All patients undergoing large-volume paracentesis
    • Patients with hypotension, hyponatremia, and/or AKI.
    • See “PPCD” for albumin dosage.

Management of refractory ascites ^[9][18][22]

Ascites is considered refractory if it does not respond to treatment or recurs after therapeutic paracentesis despite dietary sodium restriction and high-dose diuretic therapy. The following recommendations apply to refractory ascites in patients with cirrhosis.

• Rule out transient refractoriness to diuretic therapy.
• Optimize medications and ensure adherence to a low-sodium diet.
  • Patients who are on beta blockers:
    • Monitor blood pressure and renal function.
    • Consider dosage adjustment or discontinuation of beta-blockers if severe hypotension, hyponatremia, or renal dysfunction develops.
  • Consider midodrine or a vaptan on a case-by-case basis. ^[5][9][23]
  • Consider discontinuing diuretic therapy if urine Na⁺ excretion is < 30 mEq/d. ^[18]
• Repeat large-volume paracentesis (with IV albumin).
• Evaluate for invasive management options in consultation with specialists.
  • Transjugular intrahepatic portosystemic shunt (TIPS) ^[5][9]
  • Liver transplant: patients with significant liver dysfunction and/or failed TIPS ^[24]
  • Peritoneovenous shunt: patients with refractory ascites who are not candidates for paracentesis, TIPS, or liver transplant

Half of all patients with cirrhosis who develop refractory ascites die within a year. Do not delay referral for surgical management. ^[9]

• Abdominal wall hernias (e.g., umbilical, inguinal, or incisional hernias)
• Spontaneous bacterial peritonitis
• See also: “Complications of cirrhosis”

We list the most important complications. The selection is not exhaustive.

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